Abstract
Objective: The aim of present study was to investigate whether hypoxia-reoxygenation (H/R)-induced necrotizing enterocolitis (NEC) was due to increased apoptosis of the intestinal mucosa in the young mice and whether pre-treatment of the animals with recombinant human Insulin-like growth factor-I (IGF-I), known anti-apoptotic factor, could protect the intestinal cells from H/R-induced apoptosis or intestinal injury.
Study design: Young mice were divided into three groups; Group 1 mice (H/R) were hypoxia-reoxygenation; Group 2 mice (H/R + IGF-I) were treated with recombinant human IGF-I by intraperitoneal injection (1 μg/g BW; once daily) for 7 days; Group 3 mice were served as control. Hypoxia was induced by placing young mice in Plexiglas chamber, consisting 10% oxygen for 60 min. After hypoxia, the young mice were reoxygenated for 10 min with 100% oxygen. Intestinal generation of substances reactive to thiobarbituric acid (TBARS) and active caspase-3 were measured in H/R-induced intestinal injury.
Results: Increased numbers of apoptotic cells (apoptotic index) across the villi in young mice subjected to H/R were observed with the TUNEL reaction whereas few apoptotic cells existed in the control animals. In addition, H/R-induced intestinal damage in H/R + IGF-I group was greatly attenuated, with necrosis limited partially to the mucosa. Tissue active caspase-3 levels in H/R group were found to be significantly higher when compared with that of H/R + IGF-I group of mice and control. However, TBARS concentrations in the intestine were similar in H/R groups when compared to the intestine of control animals.
Conclusion: The present study suggests that both necrosis and apoptosis via mechanisms occurring oxygen-derived free radicals and activation of caspase-3 play a role in the pathogenesis of H/R-induced NEC. We also show that IGF-I protect intestinal mucosa from necrosis and apoptosis from intestinal H/R injury.
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Akisu, M., Ozen, S., Baka, M. et al. 4 Insulin-Like Growth Factor Attenuates Apoptosis and Mucosal Damage in Hypoxia/Reoxygenation-Induced Experimental Necrotizing En-Terocolitis. Pediatr Res 56, 464 (2004). https://doi.org/10.1203/00006450-200409000-00027
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DOI: https://doi.org/10.1203/00006450-200409000-00027
